Invasive Oral Tongue Mucormycosis Rapidly Presenting After Orthotopic Liver Transplant

A 68-year-old male with a history of hepatitis C cirrhosis and hepatocellular carcinoma treated with transarterial chemoembolization presented in septic shock secondary to cholangitis requiring a staged orthotopic liver transplant (OLT). On the day of the first stage of his OLT, he received a dose of Basiliximab, a chimeric mouse-human monoclonal antibody against interleukin-2T cell receptors. His absolute neutrophil count also reached a nadir of 1.4 × 10³/uL but normalized the next day. Four days later, he was given 20 mg of prednisone followed by the last stage of his transplantation. He was then started on daily tacrolimus. The very next day, before reaching therapeutic levels of tacrolimus, he was noted to have dark discoloration of his anterior oral tongue. This remained stable over the next 4 days, but given its lack of resolution, head and neck surgery was consulted to evaluate and biopsy. Figure 1 demonstrates the patients grossly necrotic oral tongue lesion. Within 24 hours, biopsy results were noted to be consistent with invasive oral tongue mucormycosis. Computed tomography sinus was clear of any sinus disease. The patient was then taken urgently for partial glossectomy and tracheostomy. Final surgical pathology, as shown in Figures 2 and 3, demonstrated necrosis and numerous fragments of broad nonseptate fungal organisms, consistent with invasive oral tongue mucormycosis. Surgical margins were clear. The patient was then placed on amphotericin B liposome and caspofungin with good response. The mucormycosis did not return, however, the patient expired 1 month later from cardiogenic versus septic shock.

Figure 1.

In situ grossly necrotic oral tongue. Intraoperative image depicting isolated grossly necrotic anterior oral tongue with black eschar just before wide local excision. Anterior aspect of oral tongue was excised using monopolar cautery until healthy well-perfused tongue remained posteriorly.

Figure 2.

Histologically necrotic tongue specimen. A, Low-power view showing necrotic tongue tissues; hematoxylin and eosin (H&E) stain, ×4 objective. B, Higher magnification reveals necrotic skeletal muscle and fibroconnective tissue with loss of nuclei; H&E, ×40 objective.

Figure 3.

Pathological evidence of invasive fungal disease. Focally there are degenerated broad fungal hyphae without obvious septation consistent with a Rhizopus subspecies (black arrows); H&E, ×40 objective.

Mucorales fungi, of the class Zygomycetes, cause the life-threatening fungal infection known as mucormycosis. Mononuclear and polymorphonuclear phagocytes are responsible for killing mucor subspecies in the immunocompetent host. Invasive mucormycosis increasingly affects immunocompromised patients with predisposing conditions, including organ transplantation, poorly controlled diabetes mellitus, malignancy, neutropenia, and iron overload. ^{1 –3} The estimated prevalence of mucormycosis among solid organ transplantation (SOT) recipients ranges from 0.4% to 16.0%, with incidence of 0% to 1.6% in liver transplant recipients. ² The mortality rate in SOT recipients with mucormycosis is high, typically ranging from 49% to 72.7%. ^4,5 The mortality of patients with mucormycosis infections after liver transplantation was 62.5% based on the literature review by Davari et al. ⁶ The incidence of invasive mucormycosis in the United States has been estimated at about 500 cases per year. ⁷ What was once a community-acquired disease, it is increasingly nosocomial in the setting of malignancy or iatrogenic immunosuppression. ⁸ More alarming is the apparent implication of wooden tongue depressors and prophylactic antifungal therapy such as itraconazole or voriconazole. ^{9 –11}

The clinical hallmark of this opportunistic fungal infection is vascular invasion resulting in thrombosis and tissue necrosis. Rhinocerebral mucormycosis is the most common form of the disease accounting for one-third to one-half of all mucormycosis cases and is most commonly (70%) associated with diabetes. Cutaneous mucormycosis can occur when the normal protective cutaneous barrier is disrupted, such as from burns, trauma, or maceration. Alarmingly, it has even been described in association with insulin injection sites, catheter insertion sites, and the tape securing the endotracheal tube in a ventilated patient. ³ Successful treatment of invasive mucormycosis requires rapid diagnosis, reversal of predisposing variables, urgent surgical debridement, and aggressive antifungal therapy.

This peculiar case is most analogous to cutaneous mucormycosis except that it involves the mucosa and muscle of the oral tongue. This patient had been in and out of hospitals for some time and thus nosocomial colonization with mucor subspecies cannot be excluded. The rapid time course of this patient’s presentation with mucormycosis has never been reported and does not have a clear singular explanation. Rather the combination of potential predisposing factors may have resulted in this unique clinical presentation. Namely, momentary neutropenia, immunosuppression with multiple agents (eg, prednisone, baciliximab, tacrolimus) albeit not concurrently, prophylactic antifungal therapy with voriconazole, and recurrent oral instrumentation (eg, endotracheal tube, transesophageal echocardiogram) with repeat visits to the operating room.

Davari et al described 51 cases of mucormycosis developing postliver transplant. They attribute the occurrence to poor transplant candidates, prolonged antibiotic therapy and presurgical hospitalization, and poor aseptic operative techniques. Among these cases, the far majority occurred at least 7 or more days following transplantation, with only one reported to have occurred as soon as 3 days postoperatively. ⁶ Additionally, only 4 other reported cases of supposed oral tongue mucormycosis have been reported. ^{12 –15} As such, a high clinical suspicion and rapid surgical and medical intervention were key to avoiding disease-specific mortality in this unique case.